Beta blockers can repair malformed blood vessels in the brain
Propranolol, a drug that is efficacious against infantile haemangiomas (“strawberry naevi”, resembling birthmarks), can also be used to treat cerebral cavernous malformations, a condition characterised by misshapen blood vessels in the brain and elsewhere. This has been shown by IGP researchers in a new study published in the scientific journal Stroke.
“Up to now, there’s been no drug treatment for these patients, so our results may become hugely important for them,” says Peetra Magnusson who headed the study.
Cerebral cavernous malformations (CCMs, also called cavernous angiomas or cavernomas) are vascular lesions on blood vessels in the brain and elsewhere, caused by genetic changes that may be hereditary or arise spontaneously. Today, an operation to remove these lesions is the only possible treatment. However, surgical interventions in the brain are highly risky. Since the vascular malformations, moreover, recur in the hereditary form of the condition, a drug treatment for CCMs is urgently required instead.
The uses of propranolol, a beta blocker, include treating cardiovascular diseases and conditions, such as high blood pressure. But it can also be used to treat a haemangioma (“strawberry naevus”), a common blood-vessel malformation in children. There are some indications that the preparation might work against CCMs as well.
The new study is a collaboration involving researchers at Uppsala University, the Swedish University of Agricultural Sciences and, in Italy, IFOM - The FIRC Institute of Molecular Oncology and the Mario Negri Institute of Pharmacological Research. The researchers have been investigating how propranolol affects the emergence of vascular lesions in the form of CCMs.
“We examined mice with vascular malformations in the brain – cavernomas or CCMs, as they’re called – that corresponded to the hereditary form of the condition in humans. The mice were given propranolol in their drinking water, and we were able to see that the cavernomas were becoming fewer and smaller. The blood vessels functioned better, too, with less leaking and improved contacts between their cells,” says Peetra Magnusson.
The propranolol dose administered to the animals was equivalent to the dose used to treat diseases in humans. Using an electron microscope, the researchers were able to study in detail how the drug affected the cavernomas. The results show that propranolol can be used to shrink and stabilise vascular lesions, and may be a potential medicine for treating CCMs.
“What makes the study especially interesting is that right now, in Italy, a clinical study is under way in which CCM patients are to get two years’ treatment with propranolol. During this period, they’re being monitored by means of magnetic resonance imaging of the blood vessels, to see how the malformations are developing,” says Elisabetta Dejana who has been working on the new study, and is also taking part in the ongoing clinical study in Italy.
Oral contraceptives and hormone treatment increase stroke risk
A new study from IGP show that oral contraceptives and also hormone replacement therapy at menopause increase the risk of stroke. The increased risk was largest during the first year of treatment, after which it declined. The study, which is now published in the journal Stroke, is based on data from more than a quarter of a million women from the database UK Biobank.
Rare genetic variants are not the main cause of common diseases
Although some rare variants can significantly increase the risk of disease for a few individuals, the majority of the genetic contribution to common diseases is due to a combination of many common genetic variants with small effects. This is shown by researchers at IGP and other departments at Uppsala University in a new comprehensive study published in the journal Nature Communications.
Subgroups of brain tumours associated with cell origin and disease prognosis
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Armed CAR-T cells to better fight cancer
Immunotherapy is increasingly becoming a successful way to treat cancer. Researchers at IGP have now developed armed CAR-T cells that reinforce the immune defence against cancer and that could increase the possibilities to successfully treat solid tumours. The study has been published in the journal Nature BioMedical Engineering.
Inflammation and net-like protein structures in cerebral cavernous malformations
In the condition known as cavernoma, lesions arise in a cluster of blood vessels in the brain, spinal cord or retina. Researchers at IGP now show in a new study that white blood cells and protein structures associated with the immune response infiltrate the vessel lesions. The findings support that inflammation has a role in the development of cavernoma and indicate a potential biomarker for the disease.
Protein landscape on cancer cells mapped with new technology
In recent years, great advances have been made in the development of new, successful immunotherapies to treat cancer. Two types of targeted immunotherapies that have revolutionised areas of cancer care are CAR T-cell therapy and antibody treatments. However, there are still significant challenges in the identification of cancer cell surface proteins that function as targets for immunotherapies. Mattias Belting, professor at Lund University and senior consultant at Skåne University Hospital, and guest professor at IGP, is well on the way and his group’s findings are now published in the journal PNAS.
CRISPR-Cas9 can generate unexpected, heritable mutations
CRISPR-Cas9, the “genetic scissors”, creates new potential for curing diseases; but treatments must be reliable. In a new study, researchers have discovered that the method can give rise to unforeseen changes in DNA that can be inherited by the next generation. These scientists therefore urge caution and meticulous validation before using CRISPR-Cas9 for medical purposes.
New technology to study DNA in archived tissue samples
Researchers at IGP have developed a technology that allows studies of DNA profiles in archived tissue samples. The technology permits investigators to better understand regulation of gene activity in cancer and precision medicine.
New genes associated with relapse of acute myeloid leukemia
In the blood cancer type acute myeloid leukemia, it is common that patients relapse some time after treatment. Researchers from IGP have in a new study identified genes that seem to be associated with the risk of relapse. The findings may form the basis for new treatment strategies and contribute to better survival for patients with acute myeloid leukemia.